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ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.
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ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.

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what is cancer?, History,Malignent tumor, non-malignent tumor(benign tumor),Largest tumor ever removed, tumour growth kinitics, doubling tume, angiogenesis, causes of cancer, drugs, treatment of …

what is cancer?, History,Malignent tumor, non-malignent tumor(benign tumor),Largest tumor ever removed, tumour growth kinitics, doubling tume, angiogenesis, causes of cancer, drugs, treatment of cancer, classification of anti-cancer agents, mechanism of actions,alkylating agents,anti metabolites, vinka alkaloids, best ways to reducing cancer.
BY P. RAVISANKAR
VIGNAN PHARMACY COLLEGE
VADLAMUDI
GUNTUR
ANDHRA PRADESH
INDIA.

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  • 1. ANTINEOPLASTIC AGENTS(anticancer drugs)P.Ravi sankarM.pharm.,(Ph.D.,)Vignan pharmacy college,VadlamudiProf.P.RavisankarVignan Pharmacy collegeValdlamudiGuntur Dist.Andhra PradeshIndiabanuman35@gmail.com0091 9059994000.simbolizes Fightagainst breast cancer
  • 2. Cancer is a disease characterized byuncontrollable, irreversible, independent,autonomous, uncoordinated and relativelyunlimited and abnormal over growth of tissues.•Cancer is not a single disease. It is a group of more than 200different diseases.•Cancer may spread to other parts of the body.• currently 1 in 4 deaths in USA are due to cancer.• 1 in 17 deaths are due to lung cancer.•An estimated 2,22,520 people diagnosed lung cancer in theUnited States in 2010.•Lung cancer is the most common cancer in men.•Breast cancer is the most common cancer in women.• Around 15 lakh new cases are diagnosed every year in india.• A total of 15,96,670 new cancer cases and 5,71,950 deaths fromcancer are projected to occur in the United States in 2011.What is Cancer?
  • 3. Introduction and History•• The medical term for tumor (or) cancer is Neoplasm, which means a relativelyautonomous growth (or) un corodinated cell proliferation of body tissue.• The term Neoplasm means New growth and the process of cell proliferation iscalled Neoplasia.• The branch of medicine which deals with the excessive study of neoplasm(tumor) and its development diagnosis and treatment is called “Oncology.”• For the first time Hippocrates coined the Greek word Karkinos i.e. (crab/crayfish) for malignant breast cancer. (because enlarge or swollen veins around themresembled the limbs of crab).• The term cancer was translated from a Latin wordcarcino i.e. Crab by celsus.• Galen used ‘oncos’ to describe all tumors, the rootof the modern word ‘oncology’.
  • 4. Malignant tumours canspread from the original site andcause secondary tumours. This iscalled metastasis. They interferewith neighbouring cells and canblock blood vessels, the gut,glands, lungs etc.Malignant tumors can also destroythe correct functioning of majororgans.Non-Malignant tumor(or) benign tumor(or) also known asnon-cancerous tumor whichdoes not metastasize.Benign tumors are not usually a threat tolife. Benign tumors generally are confinedto one area.classifiedin to twocategoriesIf the cancer is localizedIt is said to be benign.If the cancerous cells invadeThe other parts of the bodyAnd set up secondary tumorsA process known as metastasis.
  • 5. Examples of Benign Tumors Papilloma - A projecting mass on the skin (for example, a wart)Adenoma - A tumor that grows in and around the glandsLipoma - A tumor in fatty tissueOsteoma - A tumor originating in the bonesMyoma - A tumor of muscle tissue Angioma - A tumor usually composed of small blood or lymph vessels (for example, abirthmark)Nevus - A small skin tumor of one variety of tissues (for example, a mole).Most Common Cancers in Children and AdultsChildren AdultsLeukemias: acute lymphocytic (lymphoblastic)almost one-third of all childhood cancers.LungBrain and Other nervous system tumor:neuroblastomaBreast (carcinoma)Lymph-node cancers (lymphomas) ColorectalBone (osteosarcoma) ProstateSoft-tissue sarcomas: rhabdomyosarcoma Skin (melanoma)Kidney: Wilms tumorEye: retinoblastomaAdrenal gland (adrenocortical carcinoma)
  • 6. • How is cancer classified?• There are five broad groups that are used to classify cancer.• Carcinomas are characterized by cells that cover internal andexternal parts of the body such as lung, breast, and colon cancer.• Sarcomas are characterized by cells that are located in bone,cartilage, fat, connective tissue, muscle, and other supportivetissues.• Lymphomas are cancers that begin in the lymph nodes and immunesystem tissues.• Leukemias are cancers that begin in the bone marrow and oftenaccumulate in the bloodstream.• Adenomas are cancers that arise in the thyroid, the pituitary gland,the adrenal gland, and other glandular tissues.
  • 7. The tumour cells generally divide faster then the normal cells, nucleic acid synthesisIs faster and so tumour cells need more of the nucleic acid building blocks.The tumour cells need more than their fair share of the building blocks andAccumulate the cytotoxic drug contain nucleophiles(disrupting theFunction of DNA directly.) more effectively.The combination therapy(the simultaneous use of various anticancer drugs withDifferent mechanism of action) is more effective than using a single drug.Advantage is increased efficiency of action and decreased toxicity.Since the cancer cells are derived from the normal cells identifying targetThat are unique to cancer cells is not easy.As a result traditional anti cancer drugs act against targets which are presentIn both types of cell.There fore the effectiveness and selectivity of such drugs is dependent on themBecoming more concentrated in cancer cells than normal cells. Cancer cells areGenerally growing faster than normal cells.so they accumulate nutrients, syntheticBuilding blocks and drugs more quickly.Unfortunately not all drugs grow rapidly. Cells in the Centre of the tumour may beDormant.Generally bone marrow cells,hair roots grow rapidly as a result they too accumulate anticancerDrugs,resulting Bone marrow toxicity is common side effect of cancer chemotherapy.Resulting weakening of the immune system and decreased resistance to infection.If the cancer patients are infectious such secondary infections can be difficult to treat.Antibacterial drugs may not be effective as they rely on the normal functioningOf the immune system.Other side effects of anti cancer drugs are impaired wound healing, loss of hair,Damage to the epithelium of GIT,depression of growth in children, sterility,nausea, kidney damage.
  • 8. Largest tumor ever removed• According to Guinness World Records, thebiggest tumor ever removed intact fromthe human body weighed in at 303pounds (137.6 kg) and measured• 3 feet (1 m) in diameter.• The tumor, located on the right ovary,was removed in 1991 during an operationperformed by Professor KatherineO’Hanlan at Stanford UniversityMedical Center in California.• The operation to remove the tumor fromthe abdomen of an unnamed 34-year-old woman took over six hoursto complete.• The pathology report concluded thatfortunately the tumor was benign. Thepatient made a full recovery, andreportedly did not seek treatment soonerdue to being bed-ridden and sufferingfrom agoraphobia (fear of open spaces).
  • 9. China’s elephant man grows world’sLargest tumor on face.(50 pounds)The man-with-no-face."CHILDREN see me and start crying," JoseMestre mumbles sadly from behind themonstrous 12lb growth that is eating hisface.51-year-old, from Portugal.Carer ... sister Guida looks afterhim.Huang ChuncaiA Chinese man recovers from surgery thatremoved part of his facial tumors, whichweigh more than 20 kilograms in total.(32 yearys old)
  • 10. Burkitts lymphoma.Multile myelomaOsteoporosis is most common Acute leukemia blood cancerBreast cancerMucosal cells ofrectumAre all cancers tumors?Yes other than blood cancer.In which part of the body cancer can’t occur?Those having dead or non living parts of hair(other than roots)Tooth enamel,nails (non living part)
  • 11. Tumor growth and kinetics• The principle difference between mature ofnormal tissue and tumors is …• The rate of cell replication i.e. proliferation formost normal tissues equals the rate of cell death(a balance is maintained between cell renewaland cell apoptosis (programmed cell death),where as in neoplasm proliferation exceeds thecell death.• Proliferation in normal tissue responds to subtlesignals that indicate when proliferation isneeded repair, regeneration or growth anddevelopment.• But ...Neoplasm seem to lack such an autoregulation of proliferation and the cellreplication rate i.e. new cells replace the old cellsby differentiation mechanism.
  • 12. Doubling time• The doubling time is the mean (“average”) interval betweensuccessive mitoses.• It is a characteristic of the particular type of tumor cell.Doubling time varies markedly among various kinds oftumors.• Burkitt’s tumor = it is approximately 24 hours.• In acute leukemia = 2 weeks.• In breast cancer = 3 months.• In multiple myeloma = 6 to 12 months.• Mucosal cells of the rectum every 24 hours.• A tumor cell becomes detectable when the number of cellsreaches about 109to 10 10cells. This requires 30 to 33doubling times.• The neoplasm becomes lethal when the population reachesabout 5x1011to 5x1012cells, after 39 to 42 doubling times.
  • 13. Cocontact inhibitionLittle bit defect cellAs the tissue growing human cellsreplicates Perfect copies of eachother(Mitosis)One of the cell Replicates little bit fasterA change in the DNA sequence with in a gene orchromosome
  • 14. Cells that are old or not functioning properly normally self destructand are replaced by new cells.However, cancerous cells do not self destruct and continue todivide rapidly producing millions of new cancerous cells.
  • 15. Occasionally due to carcinogens(cancer causing agents) one of theCell get mutated and does notrespond to normal growthcontrol mechanisms.This mutated cell undergoes furthermutations and transforms i.e.to Converts in to tumor cell whichstarts proliferating vigorously. This inturn results in a mass of abnormalcells (tissues) called tumourOr neoplasm.Persons withhereditary canceralready have thefirst mutation.Replicating like crazy.Broken DNA replicationDNA mutations.
  • 16. SIGNALS LEADING TO APOPTOSIS
  • 17. (As the tumor cellgrows it require aSteady supply ofaminoacid,carbohydrates,oxygen,nucleicacid bases,andgrowth factors.Vascular endothelialgrowth factor,fibroblast growthfactorInteractswithreceptorsstimulateLeading to the branchingAnd extention ofCapillaries process known asANGIOGENESISVascular growth factors are present in normal cells these are released when tissue hasbeen damaged. Angiogeness helps in the repair of injured tissues and is controlled byAngiogenisis inhibitors( angiostatin and thrombospondin)Unfortunately this balance is disturbed in tumour growth.Newly developing endothelial cellsRelease proteinstimulates
  • 18. When a cell breaks away from thetumor, it can be swept into thelymph system or the bloodstreamand be carried to other parts of thebody where new tumors can(Vascular endothelial growth factor and fibroblast factor FGF2)And FGF2.
  • 19. CAUSES OF CANCER• There are several agents responsible for cancerThe agents (physical, chemical and biological) which causes cancer are called carcinogens.1 Physical agents: Uv and ionizing radiations (x-ray, gamma and alpha and beta rays causecancer, uv rays of sunlight, nuclear fission. These radiations have mutagenic effect.Ex: Leukaemias, skin, lung, breast, osteosarcoma, thyroid cancer.2. Biological agents:a. Bacterial agents: peptic ulcers and chronic gastritis and if these are left untreated for along time leads to gastric cancer.b. Fungal agents: The fungus Aspergillus flavus releases aflatoxins in stored food andgrains .If this contaminated food is consumed (espicially by Hepatitis B virus infectedpatients) it leads to hepatocellular carcinoma.c. Viral agents: Cervical cancer,Burkitt’s lymphoma,hairy cell lukaemia,Haepaticcarcinoma.3. Chemical agents: Alkylating agents, The acylating agents, Polyaromatic hydrocarbons,Aniline, arsenic, Anthracenes, dimethylsulphate,diepoxybutane,acetyl imidazole,dimethyl carbamyl chloride.carcinogens like nicotine,asbestos,coaltar,benzene,aniline dyes.4. Genetic factors: Genetic inheritance plays a key role in causing some of the cancers (breastcarcinoma,retino blastinoma.5. Diet and habits: People taking rich in fats, low fibre content and stored grains.Alcoholism, smoking, chewing tobacco and betel nut .(pan,masala,Gutka)6. Hormones and Drugs: Taking excessive oestrogens during the times of pregancy(Vaginalendometrial cancer is prevalent in the girls born to the mothers)
  • 20. • 7.Epidemiological factors:a. Geographical and Racial factors:Climate, soil, diet habit and customs etc. Geneticcomposition also influence the variations in cancer.Ex: Breast cancer in prevalent in American women.Gastric carcinoma is in Japanese.b. Environmental and cultural factors: Exposure to industrialcontaminants, smoke and radioactive metals.Cancer of penis is very rare in Muslims and jews due to thecustom of circumcision and their female partners are lesslikely to suffer(prone) to cancer of cervix.c. Age and sex: High risk of cancer is incident at an older agedue to reduction in immunity. It is usually seen in 5thdecade of life.Men are more prone to lung cancer while women aresusceptible to breast cancer.
  • 21. ANTINEOPLASTIC AGENTS• Antineoplastic agents are the drugs which are used in tomanagement of malignant disease (i.e. cancer)• Antineoplastic agents are also known as Cytotoxic agents.cancer is a very difficult disease to treat. This has been because oflack of reliable diagnostic tests for the early detection and nothaving the compounds which will cure any form of cancer.Anticancer drugs used in the treatment of malignant disease whensurgery or radiotherapy is not possible or has proved ineffective.They are also employed asadjunct to surgery or Radiotherapy. They are used asthe initial treatment as in laeukaemia.Chemotherapy usually involves combinations of drugs havingdifferent targets or mechanisms of action.Traditional anticancerdrugs are generally cytotoxic(toxic to the cells) and the moremodern drugs are selective in their action.
  • 22. How is cancer diagnosed and staged?Early detection of cancer can greatly improve the odds of successful treatmentand survival. Physicians use information from symptoms and several otherprocedures to diagnose cancer.Common tests include Common tests include the following:Biopsy of the tumorBlood tests (which look for chemicals such as tumor markers)Bone marrow biopsy (for lymphoma or leukemia)Chest x-rayComplete blood count (CBC)CT scanMRI scan (magnetic resonance imaging)Extracting cancer cells and looking at them under a microscope is the onlyabsolute way to diagnose cancer. This procedure is called a biopsy.Physicians will analyze your bodys sugars, fats, proteins, and DNA at themolecular level.For example, cancerous prostate cells release a higher level of a chemicalcalled PSA (prostate-specific antigen) into the bloodstream that can bedetected by a blood test.
  • 23. TREATMENT OF CANCER• Cancer can be treated by the following means:• 1. SurgeryRobotic radical prostatectomy for prostate cancer.(3-D) view of the surgical field, at a greatlyincreased magnification, up to 15 times greater than the human eye.2. Radiation therapy.• 3.Immunotherapy.• 4.Hormonal therapy.• 5.Antibiotics.• 6.Chemotherapy.Chemotherapy is the term applied for a wide range of chemicalsubstances i.e. drugs that are employed in the treating the cancer.These drugs may act by various mechanisms likeInterfering with the replication of DNA.Inhibiting the formation of important molecules which are needed forDNA formation and inhibiting the mytotic spindle.
  • 24. Infact, most of traditional Anticancer agents now-a- daysavailablewhich increase survival time.• supress the growth of developing neoplasm• sprerading of the disease from one place to another place.• Relief of pain upto some extent• Immunosuppressive agents are also used to prolong the life oforgans and tissue transplants during surgical procedural methodsin cancer.
  • 25. Classification of Antineoplastic drugs• Cytotoxic drugs:• A. Alkylating agents :1.Mustard drugs: Mechlorethamine, Chlorambucil, Cyclophosphomide, Melphalan .2. Aziridines : Thiotepa.3. Alkyl sulphones: Busulphan.4. Nitrosoureas : Lomustine, Carmustine.ProcarbazineB.B. AntimetabolitesAntimetabolites::Purie antagonists:Purie antagonists: 6-Mercaptopurine.Folic acid antagonist:Folic acid antagonist: Methotrexate.Pyrimidine antagonist:Pyrimidine antagonist: 5-Fluorouracil.C.C. Plant productsPlant products: 1. Vinka alkaloids: 1. Vinka alkaloidsa.a. Vincristine b. Vinblastine..2.Taxanes:2.Taxanes: PacliPaclitaxel,taxel, DoceDocetaxel.taxel.D.D. AntibioticsAntibiotics: Dactinomycin, Daunorubicin, Doxorubicin, Mitomycin.: Dactinomycin, Daunorubicin, Doxorubicin, Mitomycin.E.E. RadioisotopesRadioisotopes: Radioiodine I: Radioiodine I131131, Radiophosphorus P, Radiophosphorus P3232..F. Other cytotoxic drugsF. Other cytotoxic drugs: Hydroxyurea, cisplatin.: Hydroxyurea, cisplatin.
  • 26. Mechanism of actions of anticancer agents
  • 27. Alkylating agentsAlkylating agents ::1.Mustard drugs1.Mustard drugs : Mechlorethamine,: Mechlorethamine, Chlorambucil,Chlorambucil, Cyclophosphomide, MelphalanCyclophosphomide, MelphalanNitrogen mustards get their name because they are related to thesulfur-containing mustard gases used during First world War.cyclophosphomideLauncherCH3Missile(odour resembling mustard,garlic plant hence the name given)It is a prodrug and not toxic it self. Metabolism in the liver by cytochrome p450 enzymeOxidizes the ring.ring open takes place and generate the cytotoxicAlkylating agent.Unfortunately acrolenIs toxicity to the kidneysAnd blader and results in inflammationOdema,bleading,ulceration
  • 28. Alkylating agentsContains ractive alkylGroups .These compoundsundergoes neibhobouringgroup reactionsProduce highly reactiveCarbonium ion intermeadiatesWhich form covalent bondsBy alkylation at 7thPosition of guanine in each ofThe double starnds of DNACausing crosslinking/mispairing.This interferes in theseparationof strands and preventsmitosis or arrest cellreplication.Alkylating agentsAlkylating agentsMechanism of actionAlkylation is defined as replacement of hydrogen on an atom by analkyl group.nu - H + alkyl-Y ---------- nu-alkyl + H++ Y-(highly electrophiliccompounds)
  • 29. Undergoes neibhobouring group reactions toform Stained 3 membered onium , ethyleneimminium ion orAziridinium ions,which react with guaninegroups on DNA To produce cross-linking.If second alkyl halide reacts withWater Cross linking is the major factorFirst alkylating agent used medicinallyDisplaces chloride ionHighly electrophilic ionAlkylation of DNAProcess can be repeated
  • 30. After forming highly electrophilic aziridinium ion. Alkylation of DNA can takesPlace. Since the process can be repeated.Cross linking b/n chains or within the one chain will occur.Monoalkylation of DNA guanine units is also possible.If second alkyl halide reacts with water cross linking is the major factor.(no inhibitionOf replication,and these drugs doesn’t act as antineoplastic agents.Chlormethine is highly reactive and can react with water,blood and tissues.It is too reactive to survive the oral route and has to be administered I.V.It is mainly used for Hodgkin’s lymphoma.The side reaction mention above can be reduced by lowering the reactivity ofAlkylating agent.Putting aromatic ring on the N atom instead of methyl group.The lone pair of the N interacts with the π(pi) system of the ring and is less availableTo displace the –cl ion. As a result the intermediate Aziridinium ionis less easilyFormed and strong neucleophiles such as guanine with react with it.Melphalan takes advantage of this type of property.The drug can be given orally and also it mimic the amino acid mooietyPhenylalanine. As a result this drug is more likely to be recognized as anAmino acid and taken in to cells by carrier proteins.
  • 31. ChlorambucilUses: Multiple myeloma, Lymphosarcoma,Lymphocytic leukemia, PolycythemiaveraOverian adenocarcinoma, Hodkin’s disease and in combination testicular cancer.Chlorambucil acts by cross linking of DNA which results in formation of altered proteins leading to decreasein cell division that ultimately causes death of the cell.
  • 32. BusulphanBusulphan is a cytotoxic drug belonging to the group of alklating agent. ItIs chemically, dimethane sulphonate derivative.Similar to chlorambucil.Mechanism of action:Busulphan is a bifunctional alkylating agent. In alkylation the sulphonate groups are good leaving groupsand play a similar role to the Chlorines in the nitrogen mustards..Cross-linking with busulfanSulfonate groups are good leaving groups
  • 33. Synthesis of busulphan
  • 34. Nitrasoureas:CarmustineCarmustine and lomustine are examples ofchloroethylnitrasoureasWhich are lipid soluble and can cross theblood-brain barrier. As a result they havebeen used in the treatment of braintumours andMenengeal leukaemia.The drug decomposes spontaneously in the body toform 2 active compounds ----an alkylatingagent and a Carbamoylating agent.The organic isocyanate which is formedcarbamoylates lysine residues in proteins andmay inactive DNA repair enzymes.The alkylating agent reacts initially with the O-6position of a guanine moiety in one strand ofDNA, then with the O-6 position of a guanineunit or the N-3 position of cytosine in the otherstrand to produce interstrand cross-linking.Nitrosoureas have dual mechanisms ofAction where by they alkylate DNA andCarbamoylate proteins.
  • 35. Synthesis of carmustine(formic acid)
  • 36. • Physico-chemical properties:white powder, slight odour. PH =5 to 6.0.M.P=27-300C, poorly soluble in water, freely solublein ethanol.Toxic effects: nausea, vomiting, abdominal pain,flushing, fever, chills, changes in vision,Chest pain, yellowing of skin or eyes, headache.Therapeutic uses: Brain tumours, MultipleMyloma, Hodgkin’s disease, Gastrointestinal,lung andcolon cancer when other treatment has failed.Carmustine is given I.V because of its rapidmetabolized. Lomustine can be given orally.
  • 37. Procarbazine• Procarbazine is an antineoplastic agent belonging to the class of alkylating agent.• Chemically it is a derivative of methyl hydrazine.Mechanism/mode of action:Procarbazine exerts its cytotoxic action by Converting into highly reactive alkylatingspecies azoprocarbazine which causes 0066-methylation-methylation of guanine nucleotideparticularly thymine. This results in mispairs that Encourages point mutationsduring replication cycles of DNA. Subsequently normal postreplication mismatchRepair (MMR) systems gets activated and leads to the destruction of the cells.Physico-chemical properties:Solid , slight odour,white to paleyellow colour, M.P= 2230C Very soluble in waterSoluble in methanol and ethanol.Adverse/toxic effects:Nausea, vlomiting, constipation,drymouth,drowsiness,dizziness, muscle twitching,Weakness and temporary hair loss. Severe chest pain, seizures,irregular heart beaMental changes, blood in urine or stools. Yellowing of eyes or skin.TherapeuticusesHodgkin’s lymphoma., It is also used for certain brain tumours, small-cell carcinomasOf the lung, Non –Hodgkin’s lymphomas, and malignant melanoma.
  • 38. • Procarbazine is a prodrug and thought to undergo oxidation by cytochrome P450 enzymes(ACTIVATED BY THE ENZYMES) to produce the methyl diazonium ion. This is alkylating agent .Reaction of this ion with RNA or DNA results in methylation mainly at the 06-position ofguanine. DNA fragmentation can also occur.N = N+– CH3 ----------- N2 + +CH3--SynthesisMethyl diazonium ioncondensationAlkaline hydrolysis
  • 39. ANTIMETABOLITES• Antimetabolites are agents which inhibit the enzymesinvolved in the synthesis of DNA or its nucleotide buildingblocks. This is the another method of disrupting DNAfunction.• The inhibitors involved are described as antimetabolites.Genarally the cellular components like folic acid, purines and pyrimidinesthat are Involved in the synthesis of Nuclic acids (DNA,RNA)Antimetabolites inhibit nuclic acid synthesis by Competitive inhibition ofcellular components.They achieve this by combining with specific enzyme or getting incorporatedinto the specific enzyme therebyForming inactive macromolecules and consequent cell death. They actSpecific phase of the cell cycle.
  • 40. 5-fluorouracil• It is an anticancer drug used for the treatment of breast,liver,skin cancer which inhibit enzyme directly.• 5-flurouracil is an antineoplastic agent belonging to the classof antimetabolites i.e. pyrimidine antagonist.• It is a prodrug which is converted in thebody it its active form- deoxyribonucleotide that exerts thecytotoxic effect by inhibiting the normal pyrimidine formationwhich results in the inhibition of synthesis of DNA.
  • 41. (deoxy thymidine monophosphate..Here things start toTo go wrong further reactionis impossible..Fluorine atom is there instead of hydrogenAs a result flurouracil skeleton remains covalentlyIrreversibly bound to the active site. Now thymidine synthesis terminated .
  • 42. synthesisSynthesis of 5-flurouracilFluoroxy trifluoro methaneIt is a solid, white, odourless, partially soluble in water,methanol, insoluble in diehtyl etherHaving melting point 282oC.Adverse /Toxic effects:Nausea, tiredness, diarrhoea, pigmentation of skin,mouth sores, anaemia.blurred visionLoss of appetite, rashes, hair thinning , dermatitis.Therapeutic uses5-Flurouracil is used for treating the following cancersBreast cancerLiverSkin cancerStomach, pancreatic cancer, colon and rectal cancer.Cancer of anus, bladder, cervix, endometrium, prostrate, ovaries, penis.5-
  • 43. 6-Mercaptopurine.6-Mercaptopurine is an anticancerdrug belonging to antimetaboliteclass. Chemically it is a purine 6-thiol.Mechanism of actionIt is an analogue of naturallyoccurring purine, which isessential component of DNAcalled adenine. After theintercellular conversion ofmecaptopurine to activenucleosides, it gets interferedwith nucleic acid synthesis.Both these agents converts in to a common productthio-GMP and next converts to thio- dGTPbefore incorporation intoRNA and DNArespectively.
  • 44. Synthesis.Therapeutic uses:It exhibits immunosuppressant action.This drug is used in the primarily for the treatment of acute leukaemias and more effectiveIn children than adults.Chorio carcinoma, chronic myelocytic leukeia, Non hodkin’s lymphoma, psoriatic arthritis,Polycythemia vera, Ulcerative colitis and chrohn’s disease.Dose: it is given orally at a dose of 2.5mg/kg body weight or 75 to 100 mg/sq.m BSA.
  • 45. MethotrexateMethotrexate is one of the most widely used Antimetabolites in cancer chemotherapy.Mechanism of action: Methotrexate is an antagonist of folic acid.The DHFR is an important enzyme required for the formation of THF fromDHF.In the absence of THF, the cells cannot synthesize purine and thymidinenucleotides which ultimately blocks the formation of DNA and RNA.Without DNA the cell cannot replicate and ultimately dies. The binding ofmethotrexate to DHFR is so tight that is termed as pseudoirreversible.Dihydrofolate reductaseDihydrofolic acid ------------------------------------------ Tetrahydrofolic acid.Dihydrofolate reductaseMethotrexate ---------------------------------------------- No reaction.In the cell folic acid is first of all reduced to FH2and then FH4.Methotrexate is able to inhibit the enzyme dihydrofolate reductase anddoes not allow the formation of tetrahydrofolate which has beenessential for the synthesis of purine and pyrimidine and there by checkthe Formation of DNA and RNA.
  • 46. Synthesis:
  • 47. • Physico-chemical properties:It occurs as yellow to orange brown crystalline powder.It is insoluble in waterFreely soluble in dilute solution of alkali and slightly soluble in dil.Hcl . M.P=1920c.Adverse effects:Depression of bone marrow which lead toLeucopenia,thrombocytopenia and anaemias.In low doses methotrexate is given repeatedly causes megaloblastic anaemiaand high doses produce pancytopenia.Uses:It provedes great benefit to patients suffering withChronic carcinima, the acute leukemias,osteosarcoma, and head, neck and breastcancer.Lung cancer.Acute lymphocytic leukemia and acute myelocytic leukaemia.Poriasis.Autoimmune diseases like dermatomyositis and rhuematoid arthritis.Dose: 30mg/sq.m BSA weekly in 2 divided doses for acute leukaemia.For chronic carcinomas it is given as 15-30mg/day orally for 5 days.
  • 48. Vinka alkaloidsVinblastine is a clinically useful vinka alkaloid. It is derived form the Madagascar periwinkleplant (catharanthus roseus) formerly known as Vinka rosea.The alkaloid vinblastine is made up of twoMoieties namely catharanthine and vindolineMechanism of action:Vinblastine shows its action by binding to tubulin to prevent it frompolymerizing into microtubules. Thus the drug prevents itpolymerization in microtubules. This leads to inhibition of mitoticspindle formation by arresting the mitosis at metaphase. Thus thecell division does not occur.Physicochemical properties:It is white to slightly yellow crystalline odourless powder soluble in water, methanol,ethanol, chloroform and insoluble in ether having M.P=285oC.Toxic effects:Nausea, vomiting and muscle plain, lower back pain, joint pain ,temporary hair loss, painfulurination, blood in urine or stools, dizziness, double vision may also occur, allergicreactions include rash, itching ,swelling and difficulty in breathing.
  • 49. Structure of vinblastineChemicallyit is a complex structure consisting of two polycyclic units i.e.Catharathine and vindoline.
  • 50. SAR:The presence of acetyl group is very essential for vinblastine to exhibit itAnti cancer activity. When this is hydrolysed activity gets destroyed.2. When free hydroxyl grops were acetylated the drug lost itsAntimalignant activity.3.The potency of vinblastine reduces drastically when the double bondswere initially hydrogenated and finally converted to carbinol group viareduction.
  • 51. Uses of vinblastine:1.Vinblastine has been used in combinationTherapies for the treatment of lymphomas,Testicular cancer and ovarian cancer.Hodgkin’s disease.Non-Hodgkin’s lymphomaKaposi’s sarcomaMycosis fungoides.Dose: It is administered 0.3mg/kg for 3 weeks by I.Vinfusion.
  • 52. Vincristine:Vincristine is also obtained from Catharanthus roseus,(vinca rosea)Chemically it consists of 2 polycyclic units.It is made up of 2 moieties namely catharanthine andvindoline.It binds to the tubulin and has greater affinity towardstubulin than the vinblastine.It is mainly used in combination therapy to treatAcute leukaemias, Hodgkin’s lymphoma, small cellLung carcinoma and a variety of other tumoues.
  • 53. Mechanisam of vincristine:Tubulin is a structural protein which iscrucial to cell division.Genarally when the cell is about todivideIts microtubules depolymerize to givetubulin.The tubulin is then repolymerized toform Structure called a spindlewhich then serves to push apartthe two new cells and to act as aframe work on which thechromosome of the original cellare transferred to the nuclei of thedaughter cells.Vincristine shows its action by binding to tubulin to prevent itfrom polymerizing into microtubules.
  • 54. Physicochemical properties:It is white to yellow, crystalline,odourless,Freely soluble in water insoluble in ether and having M.P=220C.Adverse effects:Loss of sleep, tendon reflexes, severe peripheral neuropathy, some time in severe cases loss ofmotor function, foot drop, ataxia, bone marrow suppression( it is less common thanvinblastine), constipation, urinary disturbances and alopecia.Vincristine is used combination therapy toVincristine is used combination therapy totreat acute leukaemias, Hodgkin’s lymphoma, small cell lung cancer.treat acute leukaemias, Hodgkin’s lymphoma, small cell lung cancer.Burkitt’s lymphomaBurkitt’s lymphomaWilm’s tumourWilm’s tumourMyeloma and neuroblastomaMyeloma and neuroblastomaKaposi’s sarcomaKaposi’s sarcomaRhabdomyosarcomaRhabdomyosarcomaBrain, lung, breast and head and neck tumours.Brain, lung, breast and head and neck tumours.Therapeutic uses:
  • 55. • The sulfur mustards, of which mustard gas (1,5-dichloro-3-thiapentane) is a member, are a class of related cytotoxic,vesicant chemical warfare agents with the ability to formlarge blisters on exposed skin. Pure sulfur mustards arecolorless, viscous liquids at room temperature. However,when used in impure form as warfare agents they areusually yellow-brown in color and have an odor resemblingmustard plants, garlic or horseradish, hence the nameMustard agents can be deployed on the battlefield viaspraying from aircraft, or more typically by means of air-dropped bombs or artillery shells. It has proved effectiveagainst entrenched troops and encampments. Withoutproper protection, mustard gas can be proved to be lethal toinfantry
  • 56. Sulfur mustards and nitrogen mustardsMechanism of toxicityMechanism of toxicityThe compound readily eliminates aThe compound readily eliminates a chloridechlorideion by intramolecularion by intramolecular nucleophilic substitutionnucleophilic substitutionto form a cyclicto form a cyclic sulfoniumsulfonium ion. This veryion. This veryreactive intermediate tends to bond to thereactive intermediate tends to bond to theguanine nucleotide in DNA strands, which isguanine nucleotide in DNA strands, which isparticularly detrimental to cellular health.Thisparticularly detrimental to cellular health.Thisalkylation can lead to cellular death andalkylation can lead to cellular death andcancer .Mustard gas is not very soluble incancer .Mustard gas is not very soluble inwater but is very soluble in fat, contributing towater but is very soluble in fat, contributing toits rapid absorption into the skinits rapid absorption into the skin
  • 57. Soldier with muster gas burns to his back
  • 58. Mustard gas• The most widely reported and, perhaps, themost effective gas of the First World War wasmustard gas, a vesicant, which was introducedby Germany in July 1917 prior to the ThirdBattle of Ypres.[4] The Germans marked theirshells yellow for mustard gas and green forchlorine and phosgene, so they called the newgas Yellow Cross Mustard gas is not aparticularly effective killing agent (though inhigh enough doses it is fatal) but can be usedto harass and disable the enemy and pollutethe battlefield. Delivered in artillery shells,mustard gas was heavier than air, and itsettled to the ground as an oily liquidresembling sherry. Once in the soil, mustardgas remained active for several days, weeks, oreven months, depending on the weatherconditions.[32]• The skin of victims of mustard gas blistered,their eyes became very sore and they began tovomit. Mustard gas caused internal andexternal bleeding and attacked the bronchialtubes, stripping off the mucous membrane.This was extremely painful and most soldiershad to be strapped to their beds. It usuallytook a person four or five weeks to die ofmustard gas exposureMustard gas was theagent of choice, with the British stockpiling40,719 tons, the Russians 77,400 tons, theAmericans over 87,000 tons and the Germans27,597 tons.[38]
  • 59. Poison gas attack using gas cylenders inworld war -1
  • 60. ALTERNATIVES FOR ANTINEOPLASTICSCancer chemotherapy is now entering a new era which can bedescribed as molecular targeted therapeutics-highly selectiveagents which target specific molecular targets that areabnormal or over expressed in the cancer cell.Progress in this era has arisen from a better understanding ofthe cellular chemistry involved in particular cancer cellsThe development of kinase inhibitors such as IMATINIB(glivec) isa much heralded illustration of this approachThe use of antibodies and gene therapy is another area ofresearch which shows huge potential.
  • 61. Finally, one of the best ways of reducingcancer is …..• Firstly…Public education campaigns are important in highlighting thedangers of smoking, because possibly as many as 30% of cancers arecaused by smoking, excessive drinking, and hazardous solvents, as wellas promoting healthy diets and lifestyles.• Secondly, another 30% of cancers are diet related that’s why everybodyshould take healthy diets and lifestyles.• The benefits of eating high-fibre foods, fruit, and vegetables are clear.• Infact, there have been various research projects aimed at identifyingthe specific chemicals in these foods which are responsible for thisprotective property. For example,• Dithiolthiones are a group of chemicals in broccoli, cauliflower, andcabbage which appear to have protective properties, one of whichinvolves the activation of enzymes in the liver to detoxify carcinogens.• Genistein is a protective compound found in soy products usedcommonly in Asian populations have a low incidence of breast, prostate,colon cancers.• Epigallocatechin gallate, an antioxidant present in green tea, is anotherpotential protective agent.• Synthetic drugs are also being investigated as possible cancerpreventives(finasteride, aspirin, ibuprofen, and difluoromethylornithine).
  • 62. Campaign Goals• Increase Awareness• Increase Screening• Reduce Incidence• Reduce Mortality• Reduce Burden• Improve Quality of Life
  • 63. PreventionYou can reduce the risk of getting a cancerous (malignant) tumor by:Eating a healthy dietExercising regularlyLimiting alcoholMaintaining a healthy weightMinimizing your exposure to radiation and toxic chemicalsNot smoking or chewing tobaccoReducing sun exposure, especially if you burn easilyCancer screenings, such as mammography and breast examination for breastcancer and colonoscopy for colon cancer, may help catch these cancers attheir early stages when they are most treatable.Some people at high risk for developing certain cancers can take medicationto reduce their risk.
  • 64. Smokers who smoke between 1 and 14 cigarettes a day have eight times the risk ofdying from lung cancer compared to non-smokers.  Smokers who smoke more than 25cigarettes a day have 25 times this risk compared to non-smokersfactsYou can see how the lung lookswithout the effects of inhalation ofsmoke.Note black specks throughoutindicative of carbon deposits frompollution.Smokers lung with cancer.  White areaon top is the cancer, this is what killedthe person.  The blackened area is justthe deposit of tars that all smokerspaint into their lungs with every puffthey take.
  • 65. Foye’s Principles Of Medicinal Chemistry 6thEdition By Thomas L Lemke/ David AWilliams.Wilson And Gisvold’s Text Book Of Organic Medicinal And Pharmaceutical Chemistry11thEdition.Medicinal Chemistry- By Alka.L.Gupta.Essentials Of Medicinal Chemistry-2ndEdition By Andrejus Korolkovas.An Introduction To Medicinal Chemistry-3rdEdition By Grahaml.Patrick.Organic Pharmaceutical Chemistry And Medicinal Chemistry. Vol 3 By J.S Qadry , S.SQadry And Rajendra Singh.Quintessence Of Medical Pharmacology By Sujit K. Chaudari.Medicinal Chemisty. Ramarao Nadendla.A Text Book Of Medicinal Chemistry Vol2 Surendra. N Pandeya.Moscow JA, Cowan KH. Biology of cancer. In: Goldman L, Ausiello D, eds. CecilMedicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier;2007:chap 187.Thun MJ. Epidemiology of cancer. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rded. Philadelphia, Pa: Saunders Elsevier;2007:chap 185.REFERENCES

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